EP2879519A1 - A method for increasing meat and milk production - Google Patents

A method for increasing meat and milk production

Info

Publication number
EP2879519A1
EP2879519A1 EP13777178.8A EP13777178A EP2879519A1 EP 2879519 A1 EP2879519 A1 EP 2879519A1 EP 13777178 A EP13777178 A EP 13777178A EP 2879519 A1 EP2879519 A1 EP 2879519A1
Authority
EP
European Patent Office
Prior art keywords
weight
livestock
olanzapine
administered
formulation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP13777178.8A
Other languages
German (de)
French (fr)
Inventor
Umit Cifter
Ali Turkyilmaz
Onur Mutlu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanovel Hayvan Sagligi UEruenleri Sanayi ve Ticaret AS
Original Assignee
Sanovel Hayvan Sagligi UEruenleri Sanayi ve Ticaret AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanovel Hayvan Sagligi UEruenleri Sanayi ve Ticaret AS filed Critical Sanovel Hayvan Sagligi UEruenleri Sanayi ve Ticaret AS
Publication of EP2879519A1 publication Critical patent/EP2879519A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep

Definitions

  • This invention relates to the use of olanzapine or a pharmaceutically acceptable salt thereof for increasing meat and milk production in livestock.
  • Olanzapine with the chemical name 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-(2,3- b)(1 ,5)benzodiazepine, is an atypical antipsychotic which is a serotonin dopamine antagonist, and is used in the treatment of schizophrenia and other psychotic disorders.
  • the chemical structure thereof is illustrated with Formula I given below.
  • EP0868185 discloses the use of olanzapine in the treatment of depression.
  • EP0910381 discloses the use of olanzapine in the treatment of pain.
  • the present invention relates to the use of olanzapine, eliminating all aforesaid problems and bringing additional advantages to the relevant prior art.
  • the main object of the present invention is to increase the meat and milk production from livestock by means of a novel use of olanzapine.
  • Another object of the present invention is to stimulate appetite in livestock by means of a novel use of olanzapine.
  • a further object of the present invention is to stimulate hyperlipidemia, increased fat, and fat storage in livestock by means of a novel use of olanzapine.
  • Another object of the present invention is to stimulate an increase in the prolactin and bovine somatotropin hormones in livestock by means of a novel use of olanzapine.
  • a further object of the present invention is to increase the meat and milk production from livestock by means of a novel use of a stable formulation of olanzapine.
  • Another object of the present invention is to increase the meat and milk production from livestock by means of a novel use of a stable injectable formulation of olanzapine.
  • a further object of the present invention is to suppress the libido in livestock by means of a novel use of an injectable stable formulation of olanzapine.
  • said novel method comprises administering olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
  • said novel method comprises administering a formulation containing olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
  • said novel method comprises administering an injectable formulation containing olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
  • said novel method comprises administering a lipid-based injectable formulation containing olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
  • the formulation administered to the livestock according to said method also comprises one or a mixture of both of fluoxetine and/or duloxetine in a pharmaceutically acceptable amount.
  • the formulation administered to the livestock according to said method comprises olanzapine in an amount of 0,05 to 0,4 mg/kgca/day.
  • the formulation administered to the livestock according to said method further comprises fluoxetine in an amount of 0,05 to 0,4 mg/kgca/day.
  • the formulation administered to the livestock according to said method comprises duloxetine in an amount of 0,05 to 0,4 mg/kgca/day.
  • the expression "mg/kgca/day” means "milligram/kilogram of live animal/day”.
  • the formulation administered to the livestock according to said method comprises polyethylene glycol as a solvent.
  • the formulation administered to the livestock according to said method comprises alpha tocopherol as an antioxidant.
  • the formulation i administered to the livestock according to said method comprises sodium hydroxide or hydrochloric acid as a pH regulator.
  • the formulation administered to the livestock according to said method comprises methylparaben as an I antimicrobial agent.
  • methylparaben e. 0.05 - 0.18 % by weight of methylparaben (antimicrobial agent).
  • Preparation method 1 Alpha tocopherol and methylparaben are dissolved in polyethylene glycol, previously heated to 50-80°C, and then cooled down. Then, olanzapine is added thereto and dispersed homogenously. The pH thereof is regulated using NaOH/HCI, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
  • Preparation method 2 Alpha tocopherol, methylparaben, and olanzapine are suspended in polyethylene glycol. The pH thereof is regulated using NaOH/HCI, cooled, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
  • methylparaben 0.05 - 0.18 % by weight of methylparaben (antimicrobial agent).
  • Preparation method 1 Alpha tocopherol and methylparaben are dissolved in polyethylene glycol, previously heated to 50-80°C, and then cooled down. Then, olanzapine plus duloxetine or fluoxetine are added thereto and dispersed homogenously. The pH thereof is regulated using NaOH/HCI, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
  • Preparation method 2 Alpha tocopherol, methylparaben, and olanzapine plus fluoxetine or duloxetine are suspended in polyethylene glycol. The pH thereof is regulated using NaOH/HCI, cooled, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
  • Preparation method A sterile lyophilized powder of olanzapine and alpha tocopherol is prepared in vials. Before use, it is reconstituted with sterile water or sesame oil and is injected intramuscularly.
  • Example 4 A sterile lyophilized powder of olanzapine and alpha tocopherol is prepared in vials. Before use, it is reconstituted with sterile water or sesame oil and is injected intramuscularly.
  • Example 4 A sterile lyophilized powder of olanzapine and alpha tocopherol is prepared in vials. Before use, it is reconstituted with sterile water or sesame oil and is injected intramuscularly.
  • Preparation method A sterile lyophilized powder of olanzapine plus duloxetine or fluoxetine and alpha tocopherol is prepared in vials. Before use, it is reconstituted with sterile water or sesame oil and is injected intramuscularly.
  • formulations can be prepared in the form of aqueous or oily solutions. Since olanzapine is not dissolved in water, a co-solvent should be used.
  • the carrier agents used in oily solutions can be sesame oil, cotton oil, peanut oil, and opium oil.
  • Nanoparticles, sterile powder fill and freeze- drying (lyophilization) systems can be prepared.
  • formulations may be present in a suspension form.
  • the active agent is not dissolved, but dispersed in the liquid carrier.
  • Liposome and emulsions can be prepared. Oil/water or water/oil or oil/water/oil emulsions can be prepared using convenient surface active agents.
  • the meat and milk production in livestock can be surprisingly increased by making use of olanzapine.
  • Said formulation also comprises fluoxetine or duloxetine or the both at the same time.
  • the libido can also be suppressed in the livestock.
  • the formulations according to the present invention feature high stability, high solubility, and high dissolution rates, and are used preferably in an injectable form.
  • the livestock show a surprisingly increased appetite, hyperlipidemia and increased fat, increased fat storage, and increased prolactin hormone and bovine somatotropin.
  • the level of the testosterone hormone is reduced in male livestock.
  • the injectable solution is administered in an amount of 10 ml and preferably 5 ml.
  • Alpha tocopherol is particularly preferred in the formulations according to the present invention, because alpha tocopherol provides better stability than other antioxidants do. Additionally, the miscibility and uniform distribution of those components composing the solution are increased.
  • the livestock are cattle, sheep, goats, rabbits, poultry, and swine.
  • the pharmaceutical formulations according to the present invention may also comprise one or more pharmaceutically acceptable excipient(s).
  • Pharmaceutically acceptable excipients include, but are not restricted to mass increasing agents, surface stabilizers, carriers/solvents, co-solvents (used to prepare aqueous systems for active agents not dissolvable in water), etc. and the mixtures thereof.
  • Suitable mass increasing agents include, but are not restricted to mannitol, lactose, sucrose, and dextran.
  • Suitable surface stabilizers include, but are not restricted to low molecular weight oligomers, surfactants, polysorbate 80, benzalkonium chloride, low viscosity hydroxypropyl cellulose (HPC or HPC-SL), HPMC, HMC, ethyl cellulose, povidone, pluronics, sodium deoxycholate, peg-phospholipids, tyloxapol and other tritones, PVP, SLS, dioctyl sulfosuccinate, gelatin, casein, lecithin, dextran, acacia gum, stearic acid, calcium stearate, glycerol monostearate, sorbitan esters, polyoxyethylene alkyl ethers, polyethylene glycols, triethanolamine, polyvinyl alcohol, poloxamers (pluronic f68, f108), poloxamines (tetronic 908, poloxamine 908)
  • Suitable carriers/solvents include, but are not restricted to water, alcohol, and oil.
  • Suitable co-solvents are used for preparing aqueous systems of active agents not dissolvable in water, and include, but are not restricted to
  • glycerin glycerin, PEG (300, 400, 3350), propylene alcohol, ethanol, Cremophor EL, Sorbitol;
  • - complex agents ⁇ -cyclodextrin, PVP, NaCMC.
  • Suitable antimicrobial agents include, but are not restricted to phenol, m-cresol, methylparaben, propylparaben, chlorobutanol, benzyl alcohol, benzalkonium chloride, thimerosal.
  • Suitable antioxidant agents include, but are not restricted to sodium bisulfite, sodium sulfite, sodium metabisulfite, sodium thiosulphate, sodium formaldehyde, ascorbic acid isomers, acetylcysteine, cysteine, thioglycerol, thioglycolic acid, thiolactic acid, thiourea, glutathione, propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, ascorbyl palmitate, a- tocopherol.
  • Suitable pH regulators/buffering agents include, but are not restricted to acetic acid/acetate, citric acid/citrate, phosphoric acid/phosphate, glutamic acid/glutamate.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Husbandry (AREA)
  • Food Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The present invention relates to a method for increasing meat and milk production in livestock, wherein olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof is administered to the livestock.

Description

Description
A METHOD FOR INCREASING MEAT AND MILK PRODUCTION Field of Invention
This invention relates to the use of olanzapine or a pharmaceutically acceptable salt thereof for increasing meat and milk production in livestock.
Background of Invention
Nowadays, with the world's population reaching 7 billions, the most pronounced problem of the humans is meeting the nutritional needs. Especially the need for meat and milk products with protein content is increasing day by day. Protein-based foods constitute the most valuable and prominent part of nutrition and the need for protein is increasing day by day. Despite the fact that some of the protein production is obtained from plants, it is mainly derived from animal-based resources. Although the nutritional needs are increasing in line with the increasing world population; water, fossil fuel and cereal resources used in breeding livestock are decreasing. These resources should be used more efficiently. Additionally, increasing the milk and meat efficiency of livestock makes up the most significant dimension of the solution.
Olanzapine, with the chemical name 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-(2,3- b)(1 ,5)benzodiazepine, is an atypical antipsychotic which is a serotonin dopamine antagonist, and is used in the treatment of schizophrenia and other psychotic disorders. The chemical structure thereof is illustrated with Formula I given below.
Formula I The olanzapine molecule was disclosed in the patent EP454436 for the first time.
The patent application EP0868185 discloses the use of olanzapine in the treatment of depression.
The patent application EP0910381 discloses the use of olanzapine in the treatment of pain.
When the increasing food requirements are considered, the vital importance can be seen of augmenting the protein-containing animal-based foodstuffs and increasing the production efficiency. The use of olanzapine for these purposes has not been disclosed in any other documents so far.
Considering these problems and needs, it becomes obvious that a novelty is required in the technical field related to augmenting meat and milk efficiency.
Object and Brief Description of Invention
The present invention relates to the use of olanzapine, eliminating all aforesaid problems and bringing additional advantages to the relevant prior art.
Accordingly, the main object of the present invention is to increase the meat and milk production from livestock by means of a novel use of olanzapine.
Another object of the present invention is to stimulate appetite in livestock by means of a novel use of olanzapine.
A further object of the present invention is to stimulate hyperlipidemia, increased fat, and fat storage in livestock by means of a novel use of olanzapine.
Another object of the present invention is to stimulate an increase in the prolactin and bovine somatotropin hormones in livestock by means of a novel use of olanzapine.
A further object of the present invention is to increase the meat and milk production from livestock by means of a novel use of a stable formulation of olanzapine.
Another object of the present invention is to increase the meat and milk production from livestock by means of a novel use of a stable injectable formulation of olanzapine. A further object of the present invention is to suppress the libido in livestock by means of a novel use of an injectable stable formulation of olanzapine.
A method for increasing meat and milk production in livestock has been developed to achieve all objects, referred to above and to emerge from the following detailed disclosure.
According to a preferred embodiment of the present invention, said novel method comprises administering olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
According to a preferred embodiment of the present invention, said novel method comprises administering a formulation containing olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
According to a preferred embodiment of the present invention, said novel method comprises administering an injectable formulation containing olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
According to a preferred embodiment of the present invention, said novel method comprises administering a lipid-based injectable formulation containing olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof to the livestock.
According to a preferred embodiment of the present invention, the formulation administered to the livestock according to said method also comprises one or a mixture of both of fluoxetine and/or duloxetine in a pharmaceutically acceptable amount.
According to a preferred embodiment of the present invention, the formulation administered to the livestock according to said method comprises olanzapine in an amount of 0,05 to 0,4 mg/kgca/day.
According to another preferred embodiment of the present invention, the formulation administered to the livestock according to said method further comprises fluoxetine in an amount of 0,05 to 0,4 mg/kgca/day. According to a preferred embodiment of the present invention, the formulation administered to the livestock according to said method comprises duloxetine in an amount of 0,05 to 0,4 mg/kgca/day. Here the expression "mg/kgca/day" means "milligram/kilogram of live animal/day".
According to another preferred embodiment of the present invention, the formulation administered to the livestock according to said method comprises polyethylene glycol as a solvent.
) According to another preferred embodiment of the present invention, the formulation administered to the livestock according to said method comprises alpha tocopherol as an antioxidant.
According to another preferred embodiment of the present invention, the formulation i administered to the livestock according to said method comprises sodium hydroxide or hydrochloric acid as a pH regulator.
According to another preferred embodiment of the present invention, the formulation administered to the livestock according to said method comprises methylparaben as an I antimicrobial agent.
Detailed Description of Invention
Example 1 :
a. 0.5 - 30 % by weight of olanzapine,
b. 20 - 99 % by weight of polyethylene glycol (solvent),
c. 0.05 - 0.075 % by weight of alpha tocopherol (antioxidant),
d. 0.5 - 5 % by weight of NaOH/HCI (pH regulator),
e. 0.05 - 0.18 % by weight of methylparaben (antimicrobial agent).
Preparation method 1 : Alpha tocopherol and methylparaben are dissolved in polyethylene glycol, previously heated to 50-80°C, and then cooled down. Then, olanzapine is added thereto and dispersed homogenously. The pH thereof is regulated using NaOH/HCI, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials. Preparation method 2: Alpha tocopherol, methylparaben, and olanzapine are suspended in polyethylene glycol. The pH thereof is regulated using NaOH/HCI, cooled, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
Example 2:
a. 0.5 - 30 % by weight of olanzapine,
b. 0.5 - 10 % by weight of fluoxetine or duloxetine,
c. 20 - 99 % by weight of polyethylene glycol (solvent),
d. 0.05 - 0.075 % by weight of alpha tocopherol (antioxidant),
e. 0.5 - 5 % by weight of NaOH/HCI (pH regulator),
f. 0.05 - 0.18 % by weight of methylparaben (antimicrobial agent).
Preparation method 1 : Alpha tocopherol and methylparaben are dissolved in polyethylene glycol, previously heated to 50-80°C, and then cooled down. Then, olanzapine plus duloxetine or fluoxetine are added thereto and dispersed homogenously. The pH thereof is regulated using NaOH/HCI, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
Preparation method 2: Alpha tocopherol, methylparaben, and olanzapine plus fluoxetine or duloxetine are suspended in polyethylene glycol. The pH thereof is regulated using NaOH/HCI, cooled, and then filtered. Following sterilization, it is filled into vials or alternatively, sterilization is performed after filling is made into vials.
Example 3:
a. 0.5 - 10 % by weight of olanzapine,
b. 20 - 99 % by weight of sesame oil (solvent),
c. 0.05 - 0.075 % by weight of alpha tocopherol (antioxidant).
Preparation method: A sterile lyophilized powder of olanzapine and alpha tocopherol is prepared in vials. Before use, it is reconstituted with sterile water or sesame oil and is injected intramuscularly. Example 4:
a. 0.5 - 30 % by weight of olanzapine,
b. 0.5 - 10 % by weight of duloxetine or fluoxetine,
c. 20 - 99 % by weight of sterile water or sesame oil (solvent),
d. 0.05 - 0.075 % by weight of alpha tocopherol (antioxidant).
Preparation method: A sterile lyophilized powder of olanzapine plus duloxetine or fluoxetine and alpha tocopherol is prepared in vials. Before use, it is reconstituted with sterile water or sesame oil and is injected intramuscularly.
The lipid-based formulations in the examples above may be long acting. Alternative Formulation Types:
1. These formulations can be prepared in the form of aqueous or oily solutions. Since olanzapine is not dissolved in water, a co-solvent should be used. The carrier agents used in oily solutions can be sesame oil, cotton oil, peanut oil, and opium oil.
2. . Reconstitutable systems can be prepared. Nanoparticles, sterile powder fill and freeze- drying (lyophilization) systems can be prepared.
3. These formulations may be present in a suspension form. The active agent is not dissolved, but dispersed in the liquid carrier.
4. Liposome and emulsions can be prepared. Oil/water or water/oil or oil/water/oil emulsions can be prepared using convenient surface active agents.
With the present invention, the meat and milk production in livestock can be surprisingly increased by making use of olanzapine. Said formulation also comprises fluoxetine or duloxetine or the both at the same time. The libido can also be suppressed in the livestock. The formulations according to the present invention feature high stability, high solubility, and high dissolution rates, and are used preferably in an injectable form. With the method according to the present invention, the livestock show a surprisingly increased appetite, hyperlipidemia and increased fat, increased fat storage, and increased prolactin hormone and bovine somatotropin. The level of the testosterone hormone is reduced in male livestock. The injectable solution is administered in an amount of 10 ml and preferably 5 ml. Thus, undesired outcomes such as abscesses and local reactions are prevented in the application site. Alpha tocopherol is particularly preferred in the formulations according to the present invention, because alpha tocopherol provides better stability than other antioxidants do. Additionally, the miscibility and uniform distribution of those components composing the solution are increased. The livestock are cattle, sheep, goats, rabbits, poultry, and swine.
The pharmaceutical formulations according to the present invention may also comprise one or more pharmaceutically acceptable excipient(s). Pharmaceutically acceptable excipients include, but are not restricted to mass increasing agents, surface stabilizers, carriers/solvents, co-solvents (used to prepare aqueous systems for active agents not dissolvable in water), etc. and the mixtures thereof.
Suitable mass increasing agents include, but are not restricted to mannitol, lactose, sucrose, and dextran.
Suitable surface stabilizers (suspending agents, carrier agents) (0.5-99%, 0.1-50%) include, but are not restricted to low molecular weight oligomers, surfactants, polysorbate 80, benzalkonium chloride, low viscosity hydroxypropyl cellulose (HPC or HPC-SL), HPMC, HMC, ethyl cellulose, povidone, pluronics, sodium deoxycholate, peg-phospholipids, tyloxapol and other tritones, PVP, SLS, dioctyl sulfosuccinate, gelatin, casein, lecithin, dextran, acacia gum, stearic acid, calcium stearate, glycerol monostearate, sorbitan esters, polyoxyethylene alkyl ethers, polyethylene glycols, triethanolamine, polyvinyl alcohol, poloxamers (pluronic f68, f108), poloxamines (tetronic 908, poloxamine 908), cationic agents (methyltrioctylammonium chloride (aliquat 336), tetrabutylammonium bromide, choline esters).
Suitable carriers/solvents include, but are not restricted to water, alcohol, and oil.
Suitable co-solvents are used for preparing aqueous systems of active agents not dissolvable in water, and include, but are not restricted to
- liquid co-solvents: glycerin, PEG (300, 400, 3350), propylene alcohol, ethanol, Cremophor EL, Sorbitol;
- surface active agents: Polysorbate 80, 20, Pluronic 68, lecithin;
- complex agents: β-cyclodextrin, PVP, NaCMC.
Suitable antimicrobial agents include, but are not restricted to phenol, m-cresol, methylparaben, propylparaben, chlorobutanol, benzyl alcohol, benzalkonium chloride, thimerosal. Suitable antioxidant agents include, but are not restricted to sodium bisulfite, sodium sulfite, sodium metabisulfite, sodium thiosulphate, sodium formaldehyde, ascorbic acid isomers, acetylcysteine, cysteine, thioglycerol, thioglycolic acid, thiolactic acid, thiourea, glutathione, propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, ascorbyl palmitate, a- tocopherol.
Suitable pH regulators/buffering agents include, but are not restricted to acetic acid/acetate, citric acid/citrate, phosphoric acid/phosphate, glutamic acid/glutamate.

Claims

1. A method for increasing meat and milk production in livestock, wherein olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof is administered to the livestock.
2. The method according to Claim 1 , wherein a formulation comprising olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof is administered to the livestock.
3. The method according to any of the preceding claims, wherein an injectable formulation comprising olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof is administered to the livestock.
4. The method according to any of the preceding claims, wherein a lipid-based injectable formulation comprising olanzapine or a pharmaceutically acceptable salt, solvate, polymorph, or a racemic mixture thereof is administered to the livestock.
5. The method according to any of the preceding claims, wherein the formulation administered to the livestock further comprises one or a mixture of both of fluoxetine and/or duloxetine in a pharmaceutically acceptable amount.
6. The method according to any of the preceding claims, wherein said injectable solution is administered in an amount of 10 ml and preferably in an amount of 5 ml.
7. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises olanzapine in an amount of 0,05 - 0,4 mg/kgca/day.
8. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises fluoxetine in an amount of 0,05 - 0,4 mg/kgca/day.
9. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises duloxetine in an amount of 0,05 - 0,4 mg/kgca/day.
10. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises the following ingredients only:
a. 0.5 - 30 % by weight of olanzapine,
b. 20 - 99% by weight of polyethylene glycol (solvent),
c. 0.05 - 0.075% by weight of alpha tocopherol (antioxidant),
d. 0.5 - 5% by weight of NaOH/HCI (pH regulator),
e. 0.05 - 0.18% by weight of methylparaben (antimicrobial agent).
11. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises the following ingredients only:
a. 0.5 - 30% by weight of olanzapine,
b. 0.5 - 10% by weight of duloxetine or fluoxetine,
c. 20 - 99% by weight of polyethylene glycol (solvent),
d. 0.05 - 0.075% by weight of alpha tocopherol (antioxidant),
e. 0.5 - 5% by weight of NaOH/HCI (pH regulator),
f. 0.05 - 0.18% by weight of methylparaben (antimicrobial agent).
12. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises the following ingredients only:
a. 0.5 - 30% by weight of olanzapine,
b. 20 - 99% by weight of sesame oil (solvent),
c. 0.05 - 0.075% by weight of alpha tocopherol (antioxidant).
13. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises the following ingredients only:
a. 0.5 - 30% by weight of olanzapine,
b. 0.5 - 10% by weight of duloxetine or fluoxetine,
c. 20 - 99% by weight of sterile water or sesame oil (solvent),
d. 0.05 - 0.075% by weight of alpha tocopherol (antioxidant).
14. The method according to any of the preceding claims, wherein the formulation administered to the livestock comprises alpha tocopherol as an antioxidant.
EP13777178.8A 2012-07-31 2013-07-29 A method for increasing meat and milk production Withdrawn EP2879519A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201208872 2012-07-31
PCT/TR2013/000248 WO2014021804A1 (en) 2012-07-31 2013-07-29 A method for increasing meat and milk production

Publications (1)

Publication Number Publication Date
EP2879519A1 true EP2879519A1 (en) 2015-06-10

Family

ID=47561783

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13777178.8A Withdrawn EP2879519A1 (en) 2012-07-31 2013-07-29 A method for increasing meat and milk production

Country Status (4)

Country Link
US (1) US20150216206A1 (en)
EP (1) EP2879519A1 (en)
EA (1) EA201590056A1 (en)
WO (1) WO2014021804A1 (en)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3812259A (en) * 1971-08-09 1974-05-21 Upjohn Co Animal feed and process
GB9009229D0 (en) 1990-04-25 1990-06-20 Lilly Industries Ltd Pharmaceutical compounds
HUP9903684A3 (en) 1995-12-22 2001-12-28 Lilly Co Eli Use of olanzapine for the preparation of pharmaceutical compositions treating depression
CN1219878A (en) 1996-03-25 1999-06-16 伊莱利利公司 Method for treating pain
US20060160750A1 (en) * 2004-01-13 2006-07-20 Krishnan K R R Compositions of an anticonvulsant and an antipsychotic drug and methods of using the same for affecting weight loss
US8133916B1 (en) * 2009-03-10 2012-03-13 Amelgo, LLC Control of milk production and mammary involution

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2014021804A1 *

Also Published As

Publication number Publication date
US20150216206A1 (en) 2015-08-06
WO2014021804A1 (en) 2014-02-06
EA201590056A1 (en) 2015-09-30

Similar Documents

Publication Publication Date Title
US10758523B2 (en) Single-dose, ready-to-use injectable formulations
US9610297B2 (en) Stabilization of vitamin B12
JP6356064B2 (en) A new therapeutic composition comprising apomorphine as an active ingredient.
JP4863867B2 (en) Controlled release system
JP2010280726A (en) Highly concentrated stable meloxicam solution
WO2013075095A1 (en) Use of amino acid supplementation for improved muscle recovery
BRPI0708692A2 (en) formulation of medicaments in liquid form containing fluorquinolones and use thereof
EP2879519A1 (en) A method for increasing meat and milk production
WO2014021803A1 (en) Use of olanzapine in animals
EP2879517A1 (en) Use of fluoxetine for increasing meat and milk production
CN105848638A (en) Long-acting ketoprofen compositions
US20150190352A1 (en) Use of fluoxetine in animals
JP2017507190A (en) Grapiprant composition and method of use thereof
CN111465412A (en) Oral pharmaceutical compositions of NK-1 antagonists
AU2012272935B2 (en) Fast dissolving azaperone granulate formulation
Heep et al. Stabilization of vitamin B 12
Heep et al. Stabilization of vitamin B 12
JP2017517536A (en) Pergolide transdermal formulation and use thereof
US10420739B1 (en) Glutaurine compositions and therapeutic uses thereof
WO2024075135A1 (en) "stable injectable compositions of glp-2 peptide"
CN104337759A (en) Preparation method and applications of veterinary injection of veterinary diclofenac sodium

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20150217

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20170201